Fuyuhiko Matsuda - Cochemist

Total synthesis of (−)-kainic acid and (+)-allo-kainic acid through SmI2-mediated intramolecular coupling between allyl chloride and an α,β-unsaturated ester

Co-reporter:Junya Suzuki;Natsumi Miyano;Shunpei Yashiro;Taiki Umezawa

Organic & Biomolecular Chemistry 2017 vol. 15(Issue 31) pp:6557-6566

Publication Date(Web):2017/08/09

DOI:10.1039/C7OB01427A

A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI2-mediated reductive coupling between allyl chloride and an α,β-unsaturated ester, although little has been reported about SmI2-promoted C–C bond formation of an allyl chloride with an α,β-unsaturated ester. Selection of either the 3,4-cis- or 3,4-trans-selective cyclization can be accomplished simply by changing the additives from NiI2 to HMPA during reductive cyclization conducted in H2O–THF. Total synthesis of (−)-kainic acid and (+)-allo-kainic acid, which are pyrrolidine alkaloids used in neuroscience and neuropharmacology as useful molecular probes, was successfully achieved by using the stereo-complementary ring closure reactions promoted by SmI2 for the construction of the 2,3,4-trisubsituted pyrrolidine scaffold of kainoids.

Total synthesis and biological activity of dolastatin 16

Co-reporter:Loida O. Casalme;Arisa Yamauchi;Akinori Sato;Julie G. Petitbois;Yasuyuki Nogata;Erina Yoshimura;Tatsufumi Okino;Taiki Umezawa

Organic & Biomolecular Chemistry 2017 vol. 15(Issue 5) pp:1140-1150

Publication Date(Web):2017/02/01

DOI:10.1039/C6OB02657E

The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.

Synthetic study on dolastatin 16: concise and scalable synthesis of two unusual amino acid units

Co-reporter:Taiki Umezawa, Akinori Sato, Yasuto Ameda, Loida O. Casalme, Fuyuhiko Matsuda

Tetrahedron Letters 2015 Volume 56(Issue 1) pp:168-171

Publication Date(Web):1 January 2015

DOI:10.1016/j.tetlet.2014.11.054

A convenient and scalable synthesis of two unusual amino acid units found in dolastatin 16, dolaphenvaline, and dolamethylleuine, is described. Dolastatin 16, which was first isolated from the sea hare Dolabella auricularia by Pettit, exhibits not only strong inhibition of growth for a variety of human cancer cell lines but also potent antifouling activity against the larvae of the barnacle Balanus amphitrite. The key element of the synthesis is an organocatalytic Mannich reaction to construct two contiguous stereocenters in the amino acid units with almost complete enantio- and diastereoselectivity.

Recent progress toward synthesis of chlorosulfolipids: total synthesis and methodology

Co-reporter:Taiki Umezawa, Fuyuhiko Matsuda

Tetrahedron Letters 2014 Volume 55(Issue 19) pp:3003-3012

Publication Date(Web):7 May 2014

DOI:10.1016/j.tetlet.2014.03.082

Chlorosulfolipids (CSLs) are an intriguing family of natural products featuring highly chlorinated linear hydrocarbon skeletons. Although CSLs were first isolated in 1962, chemical synthesis of CSLs was hampered because relevant methods for stereoselective construction of the polychlorinated motifs of CSLs were scarce. Since Carreira’s first total synthesis of the CSL mytilipin A in 2009, several groups, including our own, have reported total syntheses of CSLs. As a result of these total syntheses, important progress has been made in the development of reliable synthetic methods for stereoselective polychlorination. In this digest, we summarize the total syntheses of CSLs by focusing on synthetic methods for stereoselective polychlorination of the organic frameworks of CSLs.Figure optionsDownload full-size imageDownload as PowerPoint slide

Omaezallene from Red Alga Laurencia sp.: Structure Elucidation, Total Synthesis, and Antifouling Activity

Co-reporter:Dr. Taiki Umezawa;Yuko Oguri;Dr. Hiroshi Matsuura;Shohei Yamazaki;Masahiro Suzuki;Erina Yoshimura;Dr. Takeshi Furuta;Dr. Yasuyuki Nogata;Dr. Yukihiko Serisawa;Dr. Kazuyo Matsuyama-Serisawa;Dr. Tsuyoshi Abe;Dr. Fuyuhiko Matsuda;Dr. Minoru Suzuki;Dr. Tatsufumi Okino

Angewandte Chemie International Edition 2014 Volume 53( Issue 15) pp:3909-3912

Publication Date(Web):

DOI:10.1002/anie.201311175

Abstract

Natural antifouling products have been the subject of considerable attention. We screened marine algae for antifouling activity and discovered omaezallenes, the new bromoallene-containing natural products isolated from the red alga Laurencia sp. Described is the isolation, structure elucidation, and total syntheses of omaezallenes. The relative and absolute configurations of natural omaezallenes were unambiguously established through total synthesis. The antifouling activities and ecotoxicity of omaezallenes were also evaluated.

Omaezallene from Red Alga Laurencia sp.: Structure Elucidation, Total Synthesis, and Antifouling Activity

Co-reporter:Dr. Taiki Umezawa;Yuko Oguri;Dr. Hiroshi Matsuura;Shohei Yamazaki;Masahiro Suzuki;Erina Yoshimura;Dr. Takeshi Furuta;Dr. Yasuyuki Nogata;Dr. Yukihiko Serisawa;Dr. Kazuyo Matsuyama-Serisawa;Dr. Tsuyoshi Abe;Dr. Fuyuhiko Matsuda;Dr. Minoru Suzuki;Dr. Tatsufumi Okino

Angewandte Chemie 2014 Volume 126( Issue 15) pp:3990-3993

Publication Date(Web):

DOI:10.1002/ange.201311175

Abstract

Natural antifouling products have been the subject of considerable attention. We screened marine algae for antifouling activity and discovered omaezallenes, the new bromoallene-containing natural products isolated from the red alga Laurencia sp. Described is the isolation, structure elucidation, and total syntheses of omaezallenes. The relative and absolute configurations of natural omaezallenes were unambiguously established through total synthesis. The antifouling activities and ecotoxicity of omaezallenes were also evaluated.

Confirmation of the Configuration of 10-Isothiocyanato-4-cadinene Diastereomers through Synthesis

Co-reporter:Keisuke Nishikawa, Taiki Umezawa, Mary J. Garson, and Fuyuhiko Matsuda

Journal of Natural Products 2012 Volume 75(Issue 12) pp:2232-2235

Publication Date(Web):November 19, 2012

DOI:10.1021/np300439e

The marine sponge metabolite 10-isothiocyanato-4-cadinene (1) was first isolated by Garson et al. from Acanthella cavernosa in 2000. The same structure 1 was later reported by Wright et al. from the nudibranch Phyllidiella pustulosa and its sponge diet, but with different NMR data. The syntheses of both enantiomers of 1 were accomplished through the isothiocyanation of 10-isocyano-4-cadinene (2) previously synthesized by our group. The correct spectroscopic data and specific rotation value of the structure 1 were determined on the basis of the syntheses. The NMR data of synthetic 1 matched those of the isothiocyanate isolated by Garson and differed from those reported by Wright. The spectroscopic data and specific rotation values of 10-epi-10-isothiocyanato-4-cadinene (6) and di-1,6-epi-10-isothiocyanato-4-cadinene (8) were also established through the syntheses of these diastereomers. Structure 6 has been reported as a natural product by Mitome et al., but the NMR data for the synthetic sample of 6 differ from those of the natural isolate.

Synthesis and Biological Activity of Kalkitoxin and its Analogues

Co-reporter:Taiki Umezawa, Manabu Sueda, Takao Kamura, Teppei Kawahara, Xuerong Han, Tatsufumi Okino, and Fuyuhiko Matsuda

The Journal of Organic Chemistry 2012 Volume 77(Issue 1) pp:357-370

Publication Date(Web):November 23, 2011

DOI:10.1021/jo201951s

Total syntheses of kalkitoxin, isolated from the Caribbean Lyngbya majuscula, and its analogues, 3-epi-, 7-epi-, 8-epi-, 10-epi-, 10-nor-, and 16-nor-kalkitoxin, were achieved via oxazolidinone-based diastereoselective 1,4-addition reaction of a methyl group and efficient TiCl4-mediated thiazoline ring formation as the key steps. The biological activities of synthetic kalkitoxin and its analogues were evaluated with brine shrimp.

Asymmetric Total Synthesis of Danicalipin A and Evaluation of Biological Activity

Co-reporter:Taiki Umezawa, Masayuki Shibata, Kensuke Kaneko, Tatsufumi Okino, and Fuyuhiko Matsuda

Organic Letters 2011 Volume 13(Issue 5) pp:904-907

Publication Date(Web):February 3, 2011

DOI:10.1021/ol102882a

Asymmetric total synthesis of danicalipin A was achieved. The synthesis was characterized by diastereoselective introduction of chlorine atoms. Biological activities with synthetic danicalipin A, its enantiomer, and racemate were also evaluated toward brine shrimp. Both enantiomers of danicalipin A showed almost the same activity.

Total Synthesis of 10-Isocyano-4-cadinene and Its Stereoisomers and Evaluations of Antifouling Activities

Co-reporter:Keisuke Nishikawa, Hiroshi Nakahara, Yousuke Shirokura, Yasuyuki Nogata, Erina Yoshimura, Taiki Umezawa, Tatsufumi Okino, and Fuyuhiko Matsuda

The Journal of Organic Chemistry 2011 Volume 76(Issue 16) pp:6558-6573

Publication Date(Web):July 14, 2011

DOI:10.1021/jo2008109

The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, and determination of its absolute stereochemistry were achieved. 10-Isocyano-4-cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, intermolecular Diels–Alder reaction and samarium diiodide induced Barbier-type cyclization were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined as (1S,6S,7R,10S) by comparison of the optical rotations between natural and synthetic samples. In addition, the authors successfully synthesized 10-epi- and di-1,6-epi-10-isocyano-4-cadinene through the same synthetic pathway. Antifouling activities against Balanus amphitrite with the cadinenes were also evaluated.

Total Synthesis of 10-Isocyano-4-cadinene and Determination of Its Absolute Configuration

Co-reporter:Keisuke Nishikawa, Hiroshi Nakahara, Yousuke Shirokura, Yasuyuki Nogata, Erina Yoshimura, Taiki Umezawa, Tatsufumi Okino and Fuyuhiko Matsuda

Organic Letters 2010 Volume 12(Issue 5) pp:904-907

Publication Date(Web):February 4, 2010

DOI:10.1021/ol9027336

The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, was achieved. The cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, an intermolecular Diels−Alder reaction and a SmI2-induced Barbier-type reaction were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined to be (1S, 6S, 7R, 10S) on the basis of the total synthesis. Antifouling activities against Balanus amphitrite with both enantiomers of 10-isocyano-4-cadinene were also evaluated.

Hydroxy-Directed, SmI2-Induced Conversion of Carbohydrates into Carbocycles

Co-reporter:Toshiyuki Kan Dr.;Shinji Nara Dr.;Takashi Ozawa;Haruhisa Shirahama Dr. Dr.

Angewandte Chemie 2000 Volume 112(Issue 2) pp:

Publication Date(Web):12 JAN 2000

DOI:10.1002/(SICI)1521-3757(20000117)112:2<363::AID-ANGE363>3.0.CO;2-N

Unter vollständiger Stereokontrolle verläuft eine SmI₂-induzierte, Hydroxygruppen-gesteuerte Cyclisierung, die mehrfach oxygenierte sechsgliedrige Carbocyclen aus Kohlenhydraten zugänglich macht. So wurde das cis-1,3-Cyclohexandiol 3 aus dem D-Glucopyranosid-Derivat 1 in ausgezeichneter Ausbeute erhalten. Die intramolekulare Kupplung wird durch einen Ein-Elektronen-Transfer von SmI₂ auf die Formylgruppe des δ-Hydroxyaldehyds 2 initiiert, der in einer Gleichgewichtsreaktion gebildet wird.

Hydroxy-Directed, SmI2-Induced Conversion of Carbohydrates into Carbocycles

Co-reporter:Toshiyuki Kan Dr.;Shinji Nara Dr.;Takashi Ozawa;Haruhisa Shirahama Dr. Dr.

Angewandte Chemie International Edition 2000 Volume 39(Issue 2) pp:

Publication Date(Web):12 JAN 2000

DOI:10.1002/(SICI)1521-3773(20000117)39:2<355::AID-ANIE355>3.0.CO;2-U

Polyoxygenatedsix-memberedcarbocycles were derived from carbohydrates with complete stereocontrol through hydroxy-directed coupling cyclization induced by SmI₂. For example, the cis-1,3-cyclohexanediol 3 is obtained from the D-glucopyranoside derivative 1 in excellent yield. The coupling cyclization is initiated by single-electron transfer from SmI₂ to the formyl group of the δ-hydroxy aldehyde 2 generated in an equilibrium process.

Hydroxyl-Directed Intermolecular Ketone–Olefin Couplings Promoted by SmI2

Co-reporter:Fuyuhiko Matsuda;Motoi Kawatsura;Ken-ichi Hosaka;Haruhisa Shirahama

Chemistry - A European Journal 1999 Volume 5(Issue 11) pp:

Publication Date(Web):29 OCT 1999

DOI:10.1002/(SICI)1521-3765(19991105)5:11<3252::AID-CHEM3252>3.0.CO;2-D

Free hydroxyl groups significantly influence the outcome of intermolecular couplings mediated by SmI₂. For example, when the α-hydroxy ketone 1 was reductively coupled, under SmI₂ induction, with the ketyl radical acceptor ethyl crotonate, the γ-lactone 2 formed with nearly complete stereocontrol.

Total synthesis and biological activity of dolastatin 16

Co-reporter:Loida O. Casalme, Arisa Yamauchi, Akinori Sato, Julie G. Petitbois, Yasuyuki Nogata, Erina Yoshimura, Tatsufumi Okino, Taiki Umezawa and Fuyuhiko Matsuda

Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 5) pp:NaN1150-1150

Publication Date(Web):2017/01/04

DOI:10.1039/C6OB02657E

The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.